NR4A1 Inhibition As a Novel Strategy to Sensitize Homologous Recombination-Proficient Ovarian Cancer to PARP Inhibitors

Objective: Ovarian tumors frequently retain proficiency in homologous recombination (HR) DNA repair, which is linked to resistance to poly ADP-ribose polymerase inhibitors (PARPi). Identifying new strategies to improve response to PARPi in women with HR-proficient ovarian cancer is a key clinical challenge. We previously demonstrated that nuclear orphan receptor NR4A1 has pro-tumor effects in ovarian cancer cells, but the prognostic value of NR4A1 expression in patient tumors was ill-defined. Our goals were to determine whether inhibiting NR4A1 reduces efficiency of HR in ovarian cancer cells, thereby enhancing sensitivity to PARPi, and to clarify the prognostic value of NR4A1 in patient tumors.